Using procalcitonin (PCT) levels to guide intravenous antibiotic use in children hospitalised with bacterial infections does not shorten the duration of therapy compared with usual care, a large UK study finds.
Previous research had suggested that PCT – a rapid response biomarker for bacterial infection – could guide antibiotic discontinuation, but the test was not routinely used in the NHS, the study authors wrote in The Lancet Child & Adolescent Health.
In a multicentre trial at 15 hospitals in England and Wales, researchers assessed whether a PCT-guided algorithm would safely reduce the duration of antibiotic therapy in children hospitalised with confirmed or suspected bacterial infections compared with usual care, which commonly used C-reactive protein as a biomarker.
Children aged 72 hours to 18 years who were hospitalised and being treated with intravenous antibiotics for more than 48 hours were eligible for the trial.
Between 11 June 2018 and 12 October 2022, a total of 15,282 children were screened for eligibility, with 1,949 randomly assigned (1:1) to receive either current clinical management alone (usual care group) or clinical management with the addition of a PCT-guided algorithm (PCT group).
In the PCT group, plasma PCT levels were tested at baseline and every one to three days during intravenous antibiotic treatment.
Assay results were fed into an algorithm which provided guidance on antibiotic management; however, clinicians could decide to over-rule the algorithm.
PCT cost versus benefit
The study found the addition of a PCT-guided algorithm was non-inferior in terms of safety but did not reduce the duration of intravenous antibiotic use compared with usual care.
In addition, a cost-effectiveness analysis showed that PCT-guided antibiotic management was more costly than usual care.
The median intravenous antibiotic duration was 96 hours in the PCT group and 99.7 hours in the usual care group (hazard ratio 0.96 [95% CI 0.87–1.05]), data showed.
Of the 917 participants in the PCT group, 78 (9%) had at least one event covered by the composite safety outcome measure compared with 85 (9%) of 904 participants in the usual care group (estimated adjusted risk difference –0.81% [95% CI upper bound 1.11]).
Among the study limitations, the researchers noted low adherence to the PTC-guided algorithm (36% at first clinical review and 54% at any clinical review).
In addition, the four hospitals who recruited the most participants had already implemented antimicrobial stewardship programmes.
Clinician workflow challenges
Concluding, the authors recommended PCT-guided algorithms should be tested in subgroups of paediatric patients to establish whether they can reduce the duration of intravenous antibiotic treatment among patients with specific clinical characteristics.
Study chief investigator Professor Enitan Carrol, professor of paediatric infection at the University of Liverpool, UK, noted the study was a pragmatic trial in which clinicians did not have to adhere to the diagnostic algorithms.
‘Adherence to the algorithm was low in our study, and there were challenges in integrating the test into routine clinical workflows,’ he said.
‘The study highlights the importance of including behaviour change and implementation frameworks into pragmatic trial designs.’
The research, known as the ‘Biomarker-guided duration of Antibiotic Treatment in Children Hospitalised with confirmed or suspected bacterial infection’ (BATCH) trial, was led by the University of Liverpool and conducted in collaboration with Cardiff University’s Centre of Clinical Trials Research, with funding from the National Institute for Health and Care Research (NIHR).
It followed a National Institute for Health and Care Excellence recommendation for further studies to assess the effectiveness of adding PCT algorithms to guide antibiotic treatment in hospitalised adults and children with suspected or confirmed serious bacterial infections.
Late last year, a large NIHR-funded and commissioned trial in adults found PCT-monitoring could significantly reduce antibiotic overuse in sepsis.
